The proposed research project is designed to determine optimal values for transferrin saturation for use in population screening for hereditary hemochromatosis. Statistical mixture modeling will be used to develop guidelines for hemochromatosis screening regimes and to determine the frequency of the gene for hemochromatosis. Once considered to be a rare disorder, hemochromatosis is now recognized to be one of the most common autosomal recessive disorders in white populations. Substantial morbidity and mortality may result from untreated hemochromatosis; thus, early detection and treatment are essential. The Centers for Disease Control and Prevention and the College of American Pathologists now recommend regular screening for hereditary hemochromatosis. Transferrin saturation is regarded as the best single screening test for the detection of individuals at risk for the disorder. The proposed research is designed to provide a statistical foundation for the analysis of population transferrin saturations to assist in development of optimal screening regimens for hemochromatosis. To determine potential screening thresholds, probability methods will be applied to data from the third National Health and Nutrition Examination Survey (NHANES III), a cross-sectional probability sample weighted to represent the U.S. population. Statistical mixture modeling will be used to determine potential transferrin saturation screening thresholds to identify individuals for repeat testing and possible further evaluation. The actual sensitivity and specificity of these screening thresholds will then be assessed using data from a separate demonstration project, "Cost effective Hemochromatosis Survey in Primary Care", designed to identify individuals with hemochromatosis. In addition, the gene frequency for hemochromatosis for whites and ethnic subgroups will also be determined by analysis of transferrin saturation data from NHANES III. This project will have two specific aims, as follow: (1) to develop guidelines for the use of transferrin saturation and related tests in detection of individuals at risk for hemochromatosis, and (2) to determine the frequency of the gene for hemochromatosis in the United States by statistical mixture modeling of population transferrin saturation data from NHANES III. The investigators state that providing the statistical foundation for the analysis of transferrin saturations should facilitate development of optimal, cost-effective screening regimens for identification of individuals requiring further evaluation for hemochromatosis.